Neuroscience
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Studies of attention and working memory address the fundamental limits in our ability to encode and maintain behaviorally relevant information, processes that are critical for goal-driven processing. Here we review our current understanding of the interactions between these processes, with a focus on how each construct encompasses a variety of dissociable phenomena. Attention facilitates target processing during both perceptual and postperceptual stages of processing, and functionally dissociated processes have been implicated in the maintenance of different kinds of information in working memory. Thus, although it is clear that these processes are closely intertwined, the nature of these interactions depends upon the specific variety of attention or working memory that is considered.
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It has been postulated that spatial working memory operates optimally within a limited range of dopamine transmission and D1 dopamine receptor signaling in prefrontal cortex. Insufficiency in prefrontal dopamine, as in aging, and excessive transmission, as in acute stress, lead to impairments in working memory that can be ameliorated by D1 receptor agonist and antagonist treatment, respectively. Iontophoretic investigations of dopamine's influence on the cellular mechanisms of working memory have revealed that moderate D1 blockade can enhance memory fields in primate prefrontal pyramidal neurons while strong blockade abolishes them. ⋯ Elucidating the orchestration of dopamine signaling in key nodes within prefrontal microcircuitry is therefore pivotal for understanding the influence of dopamine transmission on the dynamics of working memory. Here, we explore the hypothesis that the window of optimal dopamine signaling changes on a behavioral time-scale, dependent upon current cognitive demands and local neuronal activity as well as long-term alterations in signaling pathways and gene expression. If we look under the bell-shaped curve of prefrontal dopamine function, it is the relationship between neuromodulation and cognitive function that promises to bridge our knowledge between molecule and mind.
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This article argues how dopamine controls working memory and how the dysregulation of the dopaminergic system is related to schizophrenia. In the dorsolateral prefrontal cortex, which is the principal part of the working memory system, recurrent excitation is subtly balanced with intracortical inhibition. A potent controller of the dorsolateral prefrontal cortical circuit is the mesocortical dopaminergic system. ⋯ When this cortical feedback is hypoglutamatergic, the circuit of the dorsolateral prefrontal cortex tends to be unstable, such that a slight increase in dopamine releasability causes a catastrophic jump of the dorsolateral prefrontal cortex activity from a low to a high level. This may account for the seemingly paradoxical overactivation of the dorsolateral prefrontal cortex observed in schizophrenic patients. Given that dopamine transmission is abnormal in the brains of patients with schizophrenia and working memory deficit is a core dysfunction in schizophrenia, the concept of circuit stability would be useful not only for understanding the mechanisms of working memory processing but for developing therapeutic strategies to enhance cognitive functions in schizophrenia.
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Working memory dysfunction is a core component of schizophrenia, which likely contributes substantially to the pervasive and profound cognitive deficits observed in patients with this illness. Developments in functional imaging have facilitated the investigation of the neural basis of these cognitive deficits. A strong tradition within neuropsychology has been that circumscribed lesions provide observations which constrain theoretical models, and generate testable predictions on the basis of observed relationships between structural abnormalities and behavioral dysfunction. ⋯ Empirical studies in schizophrenia research are reviewed in relation to principles of normal brain function sub-serving working memory: the functional role of the lateral prefrontal cortex, physiological response capacity constraints, inter-regional functional integration, and compensatory adaptations. However, complex heterogeneous psychiatric disorders such as schizophrenia cannot be considered akin to a pure lesion model, and there are considerable methodological challenges in interpreting disruptions of working memory in psychiatric conditions, resulting from clinical, treatment and performance related confounds. The increasing use of psychopharmacological models of disease in healthy human subjects is therefore considered as an attempt to address, or to some extent circumvent these issues.
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Working memory is a mechanism for short-term active maintenance of information as well as for processing maintained information. The dorsolateral prefrontal cortex has been known to participate in working memory. The analysis of task-related dorsolateral prefrontal cortex activity while monkeys performed a variety of working memory tasks revealed that delay-period activity is a neural correlate of a mechanism for temporary active maintenance of information, because this activity persisted throughout the delay period, showed selectivity to a particular visual feature, and was related to correct behavioral performances. ⋯ Using population vectors calculated by a population of task-related dorsolateral prefrontal cortex activities, we demonstrated the temporal change of information represented by a population of dorsolateral prefrontal cortex activities during performances of spatial working memory tasks. Cross-correlation analysis using spike firings of simultaneously isolated pairs of neurons reveals widespread functional interactions among neighboring neurons, especially neurons having delay-period activity, and their dynamic modulation depending on the context of the trial. Functional interactions among neurons and their dynamic modulation could be a mechanism of information processing in the dorsolateral prefrontal cortex.